The overall objective of this project is to obtain a more detailed description of the role of cell-cell interactions in the development of the eye. Our primary focus is the neural cell adhesion molecule (NCAM), which is abundantly expressed in the eye and believed to influence a variety of developmental events. The studies also lead to the evaluation of other CAMs, gap junctions and adherens junctions. The emphasis is on two areas: the neural retina, in particular the formation of the ganglion cell and optic fiber layers, and the lens, where the interrelationship of NCAM and specialized junctions will be evaluated. Several experimental systems will be used, including in vitro models for analyzing adhesive choices in the retina and mechanisms of lens morphogenesis and differentiation, specific molecular perturbation of both tissues in vivo using antibodies and enzymes, and the analysis of mice that have site-directed mutations in NCAM. The following specific aims are proposed: Use an assay for adhesive choices made by axons and glial cells to investigate the molecular mechanisms underlying formation of the optic fiber layer and optic nerve, 2) Continue our in vivo studies on the cellular and molecular events that lead to localization of ganglion cells at the vitreal margin of the retina and the initial appearance of axons at that site, 3) Test our hypothesis that the role of NCAM in lens formation includes promotion of gap junction and adherens junction formation, and 4) Use mutations that restrict expression of particular structural forms of NCAM to further refine our understanding of the mechanisms by which this molecule influences eye development.